Normal-Superconducting Phase Transition Mimicked by Current Noise

As a superconductor goes from the normal state into the superconducting state, the voltage vs. current characteristics at low currents change from linear to non-linear. We show theoretically and experimentally that the addition of current noise to non-linear voltage vs. current curves will create ohmic behavior. Ohmic response at low currents for temperatures below the critical temperature $T_c$ mimics the phase transition and leads to incorrect values for $T_c$ and the critical exponents $\nu$ and $z$. The ohmic response occurs at low currents, when the applied current $I_0$ is smaller than the width of the probability distribution $\sigma_I$, and will occur in both the zero-field transition and the vortex-glass transition. Our results indicate that the transition temperature and critical exponents extracted from the conventional scaling analysis are inaccurate if current noise is not filtered out. This is a possible explanation for the wide range of critical exponents found in the literature.Comment: 4 pages, 2 figure

The Current-Temperature Phase Diagram of Layered Superconductors

The behavior of clean layered superconductors in the presence of a finite electric current and in zero-magnetic field behavior is addressed. The structure of the current temperature phase diagram and the properties of each of the four regions will be explained. We will discuss the expected current voltage and resistance characteristics of each region as well as the effects of finite size and weak disorder on the phase diagram. In addition, the reason for which a weakly non-ohmic region exists above the transition temperature will be explained.Comment: 8 pages (RevTeX), 4 encapsulated postscript figure

The Changing Face of Drug-induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System

Context: Adrenal insufficiency (AI) is a life-threatening condition complicating heterogeneous disorders across various disciplines, with challenging diagnosis and a notable drug-induced component. Objective: This work aimed to describe the spectrum of drug-induced AI through adverse drug event reports received by the US Food and Drug Administration (FDA). Methods: A retrospective disproportionality analysis reporting trends of drug-induced AI was conducted on the FDA Adverse Event Reporting System (FAERS) (> 15 000 000 reports since 2004). AE reports were extracted from FAERS over the past 2 decades. Interventions included cases containing any of the preferred terms in the Medical Dictionary for Regulatory Activities describing AI, and signals of disproportionate reporting for drugs recorded in 10 or more cases as primary suspect. Results: We identified 8496 cases of AI: 97.5% serious, 41.1% requiring hospitalization. AI showed an exponential increase throughout the years, with 5282 (62.2%) cases in 2015 to 2020. We identified 56 compounds associated with substantial disproportionality: glucocorticoids (N = 1971), monoclonal antibodies (N = 1644, of which N = 1330 were associated with immune checkpoint inhibitors-ICIs), hormone therapy (N = 291), anti-infectives (N = 252), drugs for hypercortisolism or adrenocortical cancer diagnosis/treatment (N = 169), and protein kinase inhibitors (N = 138). Cases of AI by glucocorticoids were stable in each 5-year period (22%-27%), whereas those by monoclonal antibodies, largely ICIs, peaked from 13% in 2010 to 2015 to 33% in 2015 to 2020. Conclusion: We provide a comprehensive insight into the evolution of drug-induced AI, highlighting the heterogeneous spectrum of culprit drug classes and the emerging increased reporting of ICIs. We claim for the urgent identification of predictive factors for drug-induced AI, and the establishment of screening and educational protocols for patients and caregivers

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment

Purpose Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). Patients and methods Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. Results In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. Conclusions Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment

Purpose: Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT)are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). Patients and methods: Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. Results: In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. Conclusions: Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System

Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term “adrenal cortical hypofunctions”. Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy

Results and clinical interpretation of germline RET analysis in a series of patients with medullary thyroid carcinoma: The challenge of the variants of uncertain significance

Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, RET genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC. A germline RET variant was identified in 31.9% of patients affected by MTC (93.8% of those having positive family history and 14.3% of clinically sporadic cases). Subsequent target testing in relatives allowed us to identify 22 asymptomatic carriers, who could undertake appropriate screening. Overall, patients with germline RET variants differed significantly from those who tested negative by family history (p < 0.001) and mean age at MTC diagnosis (44.45 vs. 56.42 years; p = 0.010), but the difference was not significant when only carriers of moderate risk variants were considered (51.78 vs. 56.42 years; p = 0.281). Out of 12 different variants detected in 49 patients, five (41.7%) were of uncertain significance (VUS). For two of these, p.Ser904Phe and p.Asp631_Leu633delinsGlu, co-segregation and genotype/phenotype analysis, matched with data from the literature, provided evidence supporting their classification in the moderate and the highest/high risk class (with a MEN2B phenotype), respectively

Anomalous finite-size effect in superconducting Josephson junction arrays

We report large-scale simulations of the resistively-shunted Josephson junction array in strip geometry. As the strip width increases, the voltage first decreases following the dynamic scaling ansatz proposed by Minnhagen {\it et al.} [Phys. Rev. Lett. {\bf 74}, 3672 (1995)], and then rises towards the asymptotic value predicted by Ambegaokar {\it et al.} [Phys. Rev. Lett. {\bf 40}, 783 (1978)]. The nonmonotonic size-dependence is attributed to shortened life time of free vortices in narrow strips, and points to the danger of single-scale analysis applied to a charge-neutral superfluid state.Comment: 4 pages, 2 figure

Dynamic Impedance of Two-Dimensional Superconducting Films Near the Superconducting Transition

The sheet impedances, Z(w,T), of several superconducting a-Mo77Ge23 films and one In/InOx film have been measured in zero field using a two-coil mutual inductance technique at frequencies from 100 Hz to 100 kHz. Z(w,T) is found to have three contributions: the inductive superfluid, renormalized by nonvortex phase fluctuations; conventional vortex-antivortex pairs, whose contribution turns on very rapidly just below the usual Kosterlitz-Thouless-Berezinskii unbinding temperature; and an anomalous contribution. The latter is predominantly resistive, persists well below the KTB temperature, and is weakly dependent on frequency down to remarkably low frequencies, at least 100 Hz. It increases with T as e-U'(T)/kT, where the activation energy, U'(T), is about half the energy to create a vortex-antivortex pair, indicating that the frequency dependence is that of individual excitations, rather than critical behavior.Comment: 10 pages, 10 figs; subm PR

Renormalization Group Study of the Intrinsic Finite Size Effect in 2D Superconductors

Vortices in a thin-film superconductor interact logarithmically out to a distance on the order of the two-dimensional (2D) magnetic penetration depth $\lambda_\perp$, at which point the interaction approaches a constant. Thus, because of the finite $\lambda_\perp$, the system exhibits what amounts to an {\it intrinsic} finite size effect. It is not described by the 2D Coulomb gas but rather by the 2D Yukawa gas (2DYG). To study the critical behavior of the 2DYG, we map the 2DYG to the massive sine-Gordon model and then perform a renormalization group study to derive the recursion relations and to verify that $\lambda_\perp$ is a relevant parameter. We solve the recursion relations to study important physical quantities for this system including the renormalized stiffness constant and the correlation length. We also address the effect of current on this system to explain why finite size effects are not more prevalent in experiments given that the 2D magnetic penetration depth is a relevant parameter.Comment: 8 pages inRevTex, 5 embedded EPS figure